High-Dose Vitamin D Doesn't Improve Glycemic Parameters

January 27, 2016

High-dose vitamin D supplementation does not appear to improve any measure of glucose metabolism in patients with prediabetes or diet-treated type 2 diabetes, a new study suggests.

Findings from the small randomized 8-week trial were published online January 19 in Diabetes Care by PhD student Henrik Wagner, of the endocrinology and diabetes unit, department of molecular medicine and surgery, Karolinska Institute, Stockholm, Sweden, and colleagues.

While prior observational studies have shown a relatively consistent association between low serum vitamin D levels and type 2 diabetes or metabolic syndrome, data have conflicted regarding potential benefits of vitamin D supplementation.

The current study stands out because the investigators adjusted for seasonal changes in serum 25(OH)D levels and used a gold-standard hyperglycemic clamp technique to estimate insulin secretion and insulin sensitivity.

"According to the findings of our study, we see no implication for vitamin D treatment to affect glucose homeostasis in subjects with abnormal glucose tolerance," Dr Wagner and colleagues conclude.

However, Anastassios G Pittas, MD, professor of medicine in the division of endocrinology, diabetes, and metabolism, Tufts Medical Center, Boston, Massachusetts, pointed out several flaws of the study, including small size, short duration, and an unexpected improvement in the placebo group.

"Longer studies of at least 1-year duration or longer with daily doses of vitamin D3 will be more informative," Dr Pittas told Medscape Medical News.

No Effect on Glycemic Parameters

Study subjects were 44 adults with either prediabetes (impaired fasting glucose, impaired glucose tolerance, or both according to an oral glucose tolerance test), or non–drug-treated type 2 diabetes (n = 12). They were randomized to 30,000 IU vitamin D3 once weekly or placebo for 8 weeks.

Season-adjusted 25(OH)D levels were 43 nmol/L in both groups at baseline. At 8 weeks, 25(OH)D level was doubled in the vitamin-D–supplemented group (+42 nmol/L) and remained unchanged in the placebo group (+0 nmol/L).

For the primary end point — relative change from baseline in first-phase serum insulin secretion — there was a tendency to an increase in the vitamin D group and a significant increase in the placebo group, with no difference between the two groups (P = .45).

No changes in second-phase insulin secretion or insulin sensitivity within or between the groups were seen. First-phase disposition index increased in both groups, with no group difference. Second-phase disposition index showed a tendency to increase in the vitamin D group (P = .06), but there was no significant difference compared with placebo (P = .95).

There were no changes in body composition except for a small increase in percent fat mass in the vitamin D group, accompanied by a similar decrease in fat-free mass, with significant differences between groups.

There was a small reduction in median HbA1c in the vitamin D group (0.1%, P = .06), but with no significant difference vs placebo (P = .84). No other glycemic measurements showed any changes.

There was a decrease of parathyroid hormone (PTH) in the vitamin D group (28 ng/L), with a tendency toward significance by group (P = .07). Triglycerides decreased nearly significantly in the placebo group, a significant change vs the vitamin D–treated group (P = 0.02). Cholesterol and LDL decreased slightly in both groups, with no difference between the groups.

Subgroup analyses of those with the lowest basal and greatest increase in 25(OH)D levels did not change these results.

No hypercalcemia or other adverse effects of vitamin D treatment were seen compared with placebo.

Longer, Larger Study Needed?

Dr Pittas told Medscape Medical News that while the study's method to measure the outcome was "robust," nonetheless "it is not surprising that results are neutral because the study has several limitations."

For one, he said, the number of participants was very small, so the study was unlikely to be adequately powered. Moreover, "It takes 8 to 12 weeks or more for vitamin D levels to plateau and probably a bit more before we see an effect on glucose tolerance. Therefore, study duration of 8 weeks is likely inadequate."

And importantly, Dr Pittas pointed out that the improvement in disposition index in the placebo group is "inconsistent with the fact that disposition index should be worse with placebo, consistent with the natural history of prediabetes."

Dr Pittas does, however, agree with the author's conclusion that "at this point, there are not enough data to support the use of vitamin D to prevent diabetes."

He recommended that clinicians refer patients to existing trials, the largest of which is the National Institutes of Health–supported multicenter Vitamin D and Type 2 Diabetes (D2d) clinical trial, which is investigating whether vitamin D supplementation can reduce the risk of developing type 2 diabetes. Dr Pittas is D2d's principal investigator.

The study was supported by grants from the European Federation for the Study of Diabetes, the Swedish Research Council, and the Swedish Diabetes Association. Renapharma contributed to independent monitoring and Merck contributed study medication. The study authors reported no further relevant financial relationships. Dr Pittas is principal investigator of the D2d study, which is funded by the National Institutes of Health and the American Diabetes Association. He has no further relevant financial relationships.

Diabetes Care. Published online January 19, 2016. Abstract


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